Positioning Europe for the EPITRANSCRIPTOMICS challenge

The genetic alphabet consists of the four letters: C, A, G, and T in DNA and C,A,G, and U in RNA. Triplets of these four letters jointly encode 20 different amino acids out of which proteins of all organisms are built. This system is universal and is found in all kingdoms of life. However, bases in DNA and RNA can be chemically modified. In DNA, around 10 different modifications are known, and those have been studied intensively over the past 20 years. Scientific studies on DNA modifications and proteins that recognize them gave rise to the large field of epigenetic and epigenomic research. The outcome of this intense research field is the discovery that development, ageing, and stem-cell dependent regeneration but also several diseases including cancer are largely controlled by the epigenetic state of cells. Consequently, this research has already led to the first FDA approved drugs that exploit the gained knowledge to combat disease. In recent years, the ~150 modifications found in RNA have come to the focus of intense research. Here we provide a perspective on necessary and expected developments in the fast expanding area of RNA modifications, termed epitranscriptomics.SCOPUS: no.jinfo:eu-repo/semantics/publishe

Anti-cancer Drugs - Nature, Synthesis and Cell

We are in constant search for new therapeutic options to cure cancer. In this book, you can find out how scientists throughout the world deal with this problem. Readers will learn how to engage nature, chemical synthesis, and cell machinery to design new anticancer agents. Nature has already been very generous in providing us different compounds which are in widespread application. Starting from these resources, various synthetic processes are applied to create synthetic drugs which can be then obtained in large quantities. Also, the cell by itself provides different possibilities to meet the constantly increasing requirements for successful therapy. Explore the book and find out what are the new ways to fight cancer

Comparative analyses of individual and multiple alterations of p53, PTEN and p16 in non-small cell lung carcinoma, glioma and breast carcinoma samples

p53, p16 and PTEN are the most commonly altered tumor suppressor genes in human cancers. In the present study, we compared the presence of individual and multiple alterations of these tumor suppressors in non-small cell lung carcinoma (NSCLC), glioma and breast carcinoma, in order to evaluate specificity of each tumor type regarding the number of altered genes, as well as their combinations. We tested the mutational status, loss of heterozygosity and methylation status of these genes. Effects of gene alterations on patients survival were also assessed. In NSCLC samples, single gene alterations occurred rarely, while there was considerable increase in incidence of double gene alterations. Furthermore, coexistence of aberrant p53, PTEN and p16 was the most frequent and had significant adverse effect on the survival of NSCLC patients. On the contrary, in glioma and breast cancer specimens, substantial number of cases had aberrant single gene only. Moreover, glioma and breast carcinoma also differ in genotypes that were predominant. Specifically, in glioma samples, prevalent were co-alterations of PTEN and p16, followed by aberrant only PTEN. In breast cancer samples, alterations in all three genes as well as in p53 and p16 were the most common. Moreover, PTEN was altered exclusively with aberrant p53, with statistically significant correlation among them. Overall, our results suggest that NSCLC, glioma and breast cancer need different approaches in molecular diagnosis and treatment with particular attention toward the number and combination of targeted genes. (C) 2014 Elsevier Masson SAS. All rights reserved

Distribution of samples according to the level of genomic instability.

<p>Distribution of samples according to the level of genomic instability.</p

Kaplan–Meier survival curves.

<p>(<b>A</b>) Patients without alterations in <i>SGCG, HTR4, ITGB1, CPS1</i> and <i>PROS1</i> had tendency for better survival; (<b>B</b>) patients with alterations in <i>LHFPL3</i> lived significantly shorter (p = 0.04); (<b>C</b>) alterations of <i>PDE4D</i> had no impact on patients' survival (<b>D</b>) alterations of <i>INPP5A</i> had no impact on patients' survival.</p

Immunohistochemical characterization of samples.

<p>Example of anaplastic astrocytoma (WHO grade III). (<b>A</b>) Cellular tumor with increased mitotic activity (HE ×200) (<b>B</b>) Diffuse nuclear p53 positivity of tumor cells (immunostaining ×250).</p

Association of the frequency of identified genes with <i>p53</i>, <i>PTEN</i>, <i>p16</i> and <i>EGFR</i> alterations.

<p>^a Bold indicates statistically significant values;</p><p><i>LHFPL3</i>- lipoma HMGIC fusion partner-like 3; <i>SGCG</i>- sarcoglycan, gamma; <i>PDE4D</i>- cAMP-specific 3′,5′-cyclic phosphodiesterase 4D; <i>HTR4</i>-5-hydroxytryptamine (serotonin) receptor 4.^b NP, number of patients per group; </p

Identification of genetic alterations in tumor DNA fingerprints.

<p>The identity of the AP-PCR bands was determined by BLAST homology search in the NCBI GenBank and EBI Sanger databases. For each gene identified, numbers indicating beginning and the end of the region of homology in the GenBank sequence, overall sequence identity of the clone (%) and number of gaps are represented.</p